The present invention relates to a method for enhancing the resolution of a dual isotope scintigraphic image, using a filter which substantially reduces edge artifacts in the subtraction image.
Scintigraphic imaging often suffers from poor resolution due to the difficulty of distinguishing the image from background radioactivity. Even the use of radiolabeled antibodies or antibody fragments which bind specifically to markers produces by or associated with a tumor, lesion, organ or tissue has not entirely solved this problem, since only a relatively small percentage of the total injected dose of labeled antibody localizes at the site of the tumor, lesion, organ or tissue. A further complication is the fact that certain tissues and organs take up immunoglobulins non-specifically, i.e., due to factors other than specific antigen-antibody binding at the recognition site of the antibody.
In order to compensate for non-specific background, it is known to use a subtraction agent and to effect a computer processed imaging program. One example of such an approach is to label a specific antibody with Iodine-131 and to inject technetium-99m, e.g., in the form of pertechnetate or technetium-labeled human serum albumin (HSA) or technetium colloid. The pertechnetate or Tc-99m-HSA is used as a blood pool subtraction agent, while the Tc-99m-colloid accretes in the liver and is used to correct for liver background.
Typically, a gamma camera is equipped with a collimator which can separately acquire counts in a high energy window and a low energy window. There is usually some scatter from the high energy to the low energy emission window. The images from the two windows are typically processed by first correcting for downscatter by multiplying the counts from the low energy window image by a scatter correction factor, normalizing to the same number of total counts in each image, and subtracting the counts of the background agent image from those of the specific label image, to produce the corrected image.
Images produced by dual isotope subtraction are often of significantly greater clarity than those without subtraction. Moreover, it is often not possible to obtain an image of a tumor, lesion, organ or tissue without subtraction, because non-specific background radioactivity is high during the time when maximum uptake of antibody has occurred and the label is emitting high counts and the activity decreases to an unacceptably low level by the time clearance of non-specific antibody has occurred to an extent where the target/background ratio is acceptable for imaging without subtraction.
Nevertheless, dual isotope subtraction planar imaging has in the past been hampered by differences in spatial resolution, attenuation, septal penetration and scatter of the two radionuclides, especially where I-131 is used for specific labeling and Tc-99m is used as a reference agent. I-131 gives rise to substantial scatter, and the I-131 images have poorer resolution and fewer counts than the Tc-99m images. Use of a conventional subtraction method, as described above, has often produced planar images having significant edge artifacts, especially at low target/background ratios. Filters of various sorts have been used in digital processing programs for single isotope scintigraphic imaging, to enhance contrast and suppress image noise, but such filtering techniques have not been applied to dual isotope subtraction.
Various methods for background compensation have been developed, including but not limited to use of a second antibody to scavenge non-target primary antibody, as disclosed in U.S. Pat. No. 4,624,846, and use of normal immunoglobulin as a reference agent, as disclosed in U.S. Pat. Nos. 4,348,376, 4,444,744, 4,460,561 and 4,331,647, referred to collectively herein as the "Goldenberg patents", the disclosures of which are incorporated by reference herein in their entireties.
A need continues to exist for an improved method of image processing for dual isotope images that avoids the edge artifacts of conventional processing techniques and which is suited to the particular imaging system and radioisotope emission characteristics which are involved in producing the image.